virginiamycin and lincosamine

Resistance among commonly isolated Gram-positive cocci have compromised the available therapeutic regimens and require structured monitoring at the local, regional, national, and international levels. Two popular treatment classes of antimicrobials (macrolides-lincosamines-streptogramins [MLS], fluoroquinolones) have been tested against 3, 049 isolates of Streptococcus pneumoniae and enterococci from the SENTRY Antimicrobial Surveillance program. The strains were obtained from clinical cases in hospitals in the United States, Canada, and six nations (10 medical centers )in Latin America. MLS and fluoroquinolone compounds had moderate activity against vancomycin-susceptible Enterococcus faecalis only (gatifloxacin, and trovafloxacin MIC(50), 0.5 microg/ml), and quinupristin/dalfopristin was potent only against E.faecium isolates (MIC(90), 1 microg/ml(-2) microg/ml). When tested against pneumococci, gatifloxacin, trovafloxacin, sparfloxacin, and quinupristin/dalfopristin (MIC(90), < or = 1 microg/ml)were most active among the newer drugs, but vancomycin and clindamycinn inhibited > or =99.8% and 84.7% to 99.1% of strains, respectively. These results from a global resistance monitoring program should encourage rapid drug development. Based on in vitro sensitivity testing, they indicate a promising role for the treatment of emerging resistant Gram-positive cocci. The clinical role for each new agent will depend on safety profiles, rates of administration, and other issues identified during development in the clinical trials process.

Topics: Amino Sugars; Anti-Bacterial Agents; Anti-Infective Agents; Canada; Drug Resistance, Microbial; Enterococcus; Fluoroquinolones; Humans; Latin America; Macrolides; Microbial Sensitivity Tests; Sentinel Surveillance; Streptococcus pneumoniae; United States; Virginiamycin

RP59500, a semisynthetic pristinamycin combination, and 14 other antimicrobial agents were tested against 108 Legionella strains. Of the ten macrolide, lincosamine and streptogramin agents tested, the new streptogramin RP59500 ranked seventh in order of activity against Legionella pneumophila on the basis of MIC90 results as follows: clarithromycin = 14-OH clarithromycin (MIC90 0.12 mg/l) > roxithromycin > erythromycin = tylosin = virginiamycin > RP59500 (MIC90 1 mg/l) = azithromycin > dirithromycin > clindamycin (MIC90 8 mg/l). Of all 14 drugs tested in this study, rifampicin was the most potent with an MIC90 of 0.008 mg/l. In this retrospective study of Legionella strains (1981-1990 isolates), we observed no trend toward resistance to the agents investigated.

Topics: Amino Sugars; Anti-Bacterial Agents; Legionella pneumophila; Macrolides; Microbial Sensitivity Tests; Virginiamycin

The ermC gene of plasmid pE194 specifies resistance to the macrolidelincosamide-streptogramin B antibiotics. This resistance, as well as synthesis of the 29,000 dalton protein product of ermC, has been shown to be induced by erythromycin. Weisblum and his colleagues have established that macrolide resistance is associated with a specific dimethylation of adenine in 23 S rRNA. We show that pE194 specifies an RNA methylase that can utilize either 50 S ribosomes or 23 S rRNA as substrates. Synthesis of this methylase is induced by low concentrations of erythromycin, and the enzyme is produced in elevated amounts by strains carrying a high copy number mutant of pE194. The methylase comigrates with the 29K ermC product on polyacrylamide gels. The purification and some properties of this methylase are described.

Topics: Amino Sugars; Anti-Bacterial Agents; Bacillus subtilis; Drug Resistance, Microbial; Erythromycin; Mutation; Plasmids; Ribosomes; Species Specificity; tRNA Methyltransferases; Virginiamycin